DESCRIPTION:(provided by applicant) Most movements are produced by the activation of motoneurons via networks of spinal interneurons. Although much is known about the functional organization of spinal motoneurons, the interneurons are considerably less well understood. In the past few years, there has been an exciting convergence of genetic, developmental, and functional studies of interneurons. This proposal takes advantage of this convergence through studies of spinal interneurons in a new vertebrate model (zebrafish) in which genetic and optical approaches can be combined in powerful ways to study interneurons and their links to behavior. The aims are: 1) To examine the expression of transcription factors as well as markers of neurotransmitter phenotypes in spinal interneurons to test the hypothesis that individual structural and functional classes of interneurons are defined by the expression of a specific transcription factor; 2) To use in vivo imaging of neuronal activity during behavior to define which spinal interneurons are active in different axial motor behaviors and to test the hypothesis that local spinal intemeurons are shared by different behaviors, whereas the activity of intersegmental ones is restricted to particular behaviors; 3) To use imaging of spinal intemeurons to study how the interneurons in one class are recruited during increases in the frequency of swimming movements. This will test the hypothesis that there is a systematic recruitment of additional, larger interneurons in a class as the intensity of the rhythmic swimming movements increases; 4) To determine the structural and functional deficits of intemeurons in a mutant line of zebrafish (accordion) in which the normal alternation of activity on the two sides of the spinal cord is disrupted. This aim will test the hypothesis that local commissural inhibitory intemeurons, which are thought to assure alternating activity during bending movements, are disrupted in the mutant line. Each of the aims addresses a fundamental issue in the neural control of movement that will apply broadly among vertebrates. These include how the structural and functional identity of spinal interneurons is specified at a molecular level, how spinal circuits generate a variety of behaviors using the set of available interneurons, how interneurons are recruited during changes in the strength of rhythmic movements, and how genetic perturbations of interneuron function lead to particular behavioral consequences. The work is basic research in the neuronal control of movements. The establishment of the principles underlying the normal production of movements provides a foundation for understanding the disruptions that occur in disease states.